Long non-coding RNAs (lncRNAs) are characterized as having 200 nucleotides or more and not coding any protein, and several been identified as differentially expressed in several human malignancies, including breast cancer. Here, we evaluated lncRNAs differentially expressed in triple-negative breast cancer (TNBC) from a cDNA microarray data set obtained in a previous study from our group. Using in silico analyses in combination with a review of the current literature, we identify three lncRNAs as potential prognostic factors for TNBC patients. We found that the expression of WDFY3-AS2, BDNF-AS, and AFAP1-AS1 was associated with poor survival in patients with TNBCs. WDFY3-AS2 and BDNF-AS are lncRNAs known to play an important role in tumor suppression of different types of cancer, while AFAP1-AS1 exerts oncogenic activity. Our findings provided evidence that WDFY3-AS2, BDNF-AS, and AFAP1-AS1 may be potential prognostic factors in TNBC development.

CD40, a member of the tumor necrosis factor receptor (TNFR) family, is known to be involved in immune system regulation, acting as a costimulatory molecule, and in antitumor responses against cancer cells. It is a protein that is expressed in different types of cells, including immune cells and cancer cells (e.g., cervical cancer, breast cancer, melanoma). In this study, we investigated CD40/CD40L transcriptional and protein levels in cervical cancer cell lines and tumors. Higher CD40 expression was observed in cervical cancer cell lines derived from squamous cell carcinomas than from adenocarcinomas. Search of CD40/CD40L expression in cervical cancer tissues in public data sets revealed that about 83% of squamous cell carcinomas express CD40 compared to other cervical tumor subtypes. Moreover, expression of CD40 and CD40L in squamous cervical carcinomas is associated with better overall survival. Therefore, these proteins could be explored as prognostic markers in cervical cancers.

Background: Cysteine-rich secretory protein 3 (CRISP3) emerges as a potential biomarker in the study of many cancers, including cervical cancer (CC). This study aimed to analyze the expression pattern of CRISP3 in CC patients and CC cell lineages, following treatment with the epigenetic drugs: trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-aza). Methods: The differentially expressed genes identified in GSE63514 were used to construct a protein–protein interaction network. CRISP3 was selected for subsequent analyses. We utilized data from the TCGA and GENT2 projects to evaluate the expression profile and clinical behavior of CRISP3. Additionally, we conducted cell culture experiments to analyze the expression profile of CRISP3 in cells. Results: Low levels of CRISP3 were observed in squamous cell carcinoma (SCC) and human papillomavirus (HPV)16+, along with being associated with worse overall survival (OS). MIR-1229–3p was analyzed, and its high expression was associated with worse prognostic outcomes. In CC-derived cell lines, we observed low levels of CRISP3 in SiHa, followed by SW756, C33A, HeLa, and higher levels in CaSki. All cells were treated with TSA, 5-aza, or both. In all cell lines, treatment with TSA resulted in increased transcription of CRISP3. Conclusion: We identified a significant downregulation of CRISP3 in CC, particularly in cases with HPV16 infection and SCC, which was associated with poorer OS. Preliminary findings suggest that epigenetic treatments with TSA and 5-aza may modulate CRISP3 expression, warranting further research to elucidate its regulatory mechanisms and potential as a prognostic biomarker.

Objective: Breast cancer (BC) is the main cause of cancer-related deaths in women across the world. It can be classified into different subtypes, including triple-negative (TN), which is characterized by the absence of hormone receptors for estrogen and progesterone and the lack of the human epidermal growth factor receptor 2. These tumors have high heterogeneity, acquire therapeutic resistance, and have no established target-driven treatment yet. The identification of differentially expressed genes in TN breast tumors and the in silico validation of their prognostic role in these tumors. Materials and Methods: We employed a microarray dataset and, by using the GEO2R tool, we identified a list of differentially expressed genes. The in silico validation was conducted using several online platforms including the KM Plotter, cBioPortal, bc-GenExMiner, Prognoscan, and Roc Plotter. Results: We observed that FZD9 was among the top differentially expressed genes in a cohort of patients with different TNBC subtypes. The FZD9 expression was significantly different in TN breast tumors than in non-TN (nTN) breast tumors (p<0.0001), and the basal TN subtype showed the highest levels (p<0.0001). In addition, the FZD9 levels were significantly inversely and positively proportional (p<0.0001) to estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 clinical parameters. The high levels of FZD9 were associated with worse overall survival (p=0.007), relapse-free survival (p=5.8e-05), and worse survival in patients who received chemotherapy (p=3.2e-05; 0.007). Conclusion: Our cumulative results demonstrated that FZD9 plays an important role in TNBC and may be a potential prognostic biomarker. Nevertheless, further in vitro and in vivo assays are necessary to confirm our findings and to strengthen the evidences about the mechanisms by which FZD9 functions in these tumors.

Objective: Breast cancer is classified based on hormone receptor status and human epidermal growth factor receptor 2 (HER2) expression, including luminal, HER2+, or triple-negative (TNBC). The absence of a therapeutic target in TNBC and the resistance to treatment associated with other subtypes means that research for new biomarkers remains important. In this context, superoxide dismutase 2 (SOD2) has emerged as a potential therapeutic target due to its clinicopathological associations and its ability to predict responses in human tumors. To analyze SOD2 staining in samples obtained from individuals with breast cancer and explore its transcriptional pattern across tumor subtypes. Materials and Methods: SOD2 staining was assessed using the immunohistochemistry (IHC) in 80 samples from breast cancer patients. To analyze the expression profile at the transcriptional level, international databases such as cBioPortal (1,980 patients) and PrognoScan were accessed. Results: Significant differences were observed between SOD2 expression analyzed by IHC, and estrogen (p = 0.0008) and progesterone (p = 0.0003) receptors, as well as tumor subtypes (p<0.0001). These differences were found in conjunction with other associations, including clinical and pathological data, such as tumor stage (p = 0.0129), tumor size (p = 0.0296), and node metastasis (p = 0.0486). Moreover, elevated SOD2 expression correlated with an unfavorable prognosis. The in silico analysis revealed a similar pattern, despite operating at the transcriptional level. Moreover, notable correlations were identified between elevated SOD2 expression and worse survival. Conclusion: These results highlight the importance of SOD2 in breast cancer, particularly in aggressive subtypes. Increased SOD2 staining correlates with poorer outcomes, suggesting it as a potential therapeutic target.

Breast cancer is a disease that affects women worldwide, and therefore is a health problem of global concern. Despite scientific and technological advances in basic researches and in clinical studies, breast cancer still presents numerous obstacles that need to be overcome in order to ensure better survival for patients affected by this disease. Science’s work is not only to predict the best methods of treatment, but also to prevent the onset of symptoms and, consequently, of the tumor. Recent articles discuss numerous factors which may contribute to tumor initiation and progression. They take into consideration social habits, such as smoking, alcohol drinking, diets that contribute to hyperlipidemia or increased availability of antagonist molecules that act on the cell in order to create a favorable microenvironment to tumorigenesis. In addition to that, factors related to family history and hereditary predisposition are important, even though they explain a minimal portion of cases. Thus, the purpose of this article is to address modifiable and non-modifiable risk factors, related to breast cancer progression.